Abstract

Simple SummaryTumor-associated macrophages (TAMs) are a class of immune cells present in solid tumors and they are involved in cancer-related inflammation. However, to our knowledge, literature about TAMs in canine soft tissue sarcomas (STSs) is limited to absent. Here we analyzed 38 STSs retrieved from the veterinary pathology archive. Only STSs arising from limbs and the trunk were included. Oral, visceral STSs, and tumors mimicking STSs were excluded. TAMs were identified by means of immunohistochemistry and were counted in 10 consecutive tumors areas, where no confounding factors such as necrosis or other inflammatory cells could be identified. Associations between numbers of TAMs and tumor features were investigated. TAMs were evident in all STSs and ranged between 6% to 62% of the cells in the microscopic field. The number of TAMs positively correlated with the STSs’ histologic grade. The present findings suggest that TAMs are present in higher numbers when STSs are of aggressive histological grade and especially in those with a high number of proliferating cancer cells. The abundant presence of TAMs in high grade STSs may also increase the likelihood of a pathologist misdiagnosing STS for tumors where macrophages are the actual cancerous component, such as histiocytic sarcomas.Tumour-associated macrophages (TAMs) are an important part of the tumour microenvironment but knowledge of their distribution in canine soft tissue sarcomas (STSs) is limited to absent. We analysed 38 STSs retrieved from the veterinary pathology archive; oral and visceral STSs, synovial cell sarcoma, tumours of histiocytic origin, haemangiosarcoma, carcinosarcomas, and undifferentiated tumours were excluded. Iba-1 positive, non-neoplastic tumour infiltrating cells (morphologically indicative of macrophages) were classified as TAMs and were counted in 10 consecutive tumours areas, where no necrosis or other inflammatory cells could be identified. Associations between numbers of TAMs and mitoses, differentiation, and necrosis scores or grade were investigated. TAMs were evident in all STSs and ranged between 6% to 62% of the cells in the microscopic field. The number of TAMs positively correlated with the STSs’ histologic grade. When the components of the grade were analysed separately, TAMs were statistically correlated with mitoses, but not with differentiation or necrosis score. The present findings suggest that TAMs are present in higher numbers when STS proliferation is the predominant feature that drives tumour grade. The abundant presence of TAMs in high-grade STSs may also increase the likelihood of a pathologist misdiagnosing STS for histiocytic sarcoma.

Highlights

  • Non-resolving inflammation is one of the hallmarks of cancer, and among inflammatory cells, tumor-associated macrophages (TAMs) represent probably the most relevant component of the leucocytes infiltrate [1,2,3]

  • Cases were considered eligible for the study only if formalin fixed paraffin-embedded (FFPE) tissues were available for review and if neoplastic cells stained positive for vimentin, and negative for the calcium-binding adapter molecule 1 (Iba-1), Von Willebrand factor, and pan-cytokeratin

  • Iba1 immunohistochemistry successfully stained TAMs infiltrating within the soft tissue sarcomas (STSs) studied; these exhibited a predominant pleomorphic morphology with several dendriticlike cytoplasmic elongation, which embraced neoplastic cells (Figure 1a,b)

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Summary

Introduction

Non-resolving inflammation is one of the hallmarks of cancer, and among inflammatory cells, tumor-associated macrophages (TAMs) represent probably the most relevant component of the leucocytes infiltrate [1,2,3]. M2 macrophages are mainly activated by helper T-cell (Th) 2 secreted cytokines (such as interleukin (IL)-4, IL-10, and IL-13) and are thought to play a relevant role in cancer initiation and promotion, immune suppression, metastasis, and angiogenesis [1,3]. Tumor infiltration by macrophages with M1 phenotype seem to favor a better prognosis in non-small cell lung cancer and ovarian cancer [5,6], among others.

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